{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:19:02Z","timestamp":1787242742838,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 \u00b5M. Cells incubated with compounds 2c, 7h and 7l were found to show viability \u226450%, and were taken forward for dose\u2013response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 \u00b5M. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 \u00b5M, wherein compound 7h showed Chk1 inhibition at 2 and 5 \u00b5M, while pChk1 expression was observed for compound 7l at a concentration of 5 \u00b5M. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR\/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.<\/jats:p>","DOI":"10.3390\/molecules27144637","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T03:34:40Z","timestamp":1658374480000},"page":"4637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3133-601X","authenticated-orcid":false,"given":"Mykhaylo","family":"Frasinyuk","sequence":"first","affiliation":[{"name":"V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 02094 Kiev, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimple","family":"Chhabria","sequence":"additional","affiliation":[{"name":"Discipline of Chemistry, Indian Institute of Technology Gandhinagar, Gandhinagar 382055, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Kartsev","sequence":"additional","affiliation":[{"name":"InterBioScreen, 119019 Chernogolovka, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-8200","authenticated-orcid":false,"given":"Haritha","family":"Dilip","sequence":"additional","affiliation":[{"name":"Discipline of Chemistry, Indian Institute of Technology Gandhinagar, Gandhinagar 382055, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samvel N.","family":"Sirakanyan","sequence":"additional","affiliation":[{"name":"Scientific Technological Center of Organic and Pharmaceutical Chemistry, National Academy of Science of the Republic of Armenia, Institute of Fine Organic Chemistry, Yerevan 0014, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7200-7602","authenticated-orcid":false,"given":"Sivapriya","family":"Kirubakaran","sequence":"additional","affiliation":[{"name":"Discipline of Chemistry, Indian Institute of Technology Gandhinagar, Gandhinagar 382055, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-2710","authenticated-orcid":false,"given":"Anthi","family":"Petrou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9894-7777","authenticated-orcid":false,"given":"Athina","family":"Geronikaki","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cG. Ciamician\u201d, Alma Mater Studiorum-Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101084","DOI":"10.1016\/j.redox.2018.101084","article-title":"ROS and the DNA damage response in cancer","volume":"25","author":"Srinivas","year":"2019","journal-title":"Redox Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127517","DOI":"10.1016\/j.bmcl.2020.127517","article-title":"Characterization of SPK 98, a Torin2 analog, as ATR and mTOR dual kinase inhibitor","volume":"30","author":"Bhakuni","year":"2020","journal-title":"Bioorg. Med. Chem. 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